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NCT Number: NCT05526950

Cytokine Filtration in Lung Transplantation: A Swedish National Study (GLUSorb)

Lung transplantation (LTx) remains the gold standard for treating patients with irreversible end-stage pulmonary disease. Of the major organs transplanted, survival in LTx recipients remains the lowest (mean 5 years). Despite improvements, primary graft dysfunction (PGD), as defined by respiratory insufficiency and edema up to 72 hours post LTx, remains the leading cause of early mortality and contributes to the development of chronic lung allograft dysfunction (CLAD) which is the leading cause of late mortality. PGD develops within the first 72 hours after LTx. The development of CLAD increases quickly with cumulative incidence of 40-80 % within the first 3-5 years. There is a general lack of efficient treatments for PGD and CLAD. Prevention of PGD is therefore of crucial importance and has a direct impact on survival.

The present study is a randomized controlled study which aims to compare patients undergoing LTx with and without the utilization of cytokine adsorption.

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Key information

Conditions

Lung Transplant Failure Lung Transplant; Complications

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Sandra Lindstedt

Lund, Skåne County, 224 60, Sweden

Location status: Recruiting

Location contact

Jesper Magnusson, MD, PhD

SUB_INVESTIGATOR

Sandra Lindstedt

CONTACT

[email protected]

+46737220580

About this study

Early intolerance to the newly transplanted lung starts at the time of transplantation and results in PGD driven by an intense inflammatory response. Cytokines play a critical role as signaling molecules that initiate, amplify, and maintain inflammatory responses both locally and systemically. The use of cytokine filtration devices to target middle- and low-molecular weight molecules has been shown to reduce levels of a diverse number of cytokines. These results have been demonstrated in the in vitro reduction of pathogen-associated molecular pattern molecules (PAMPS) and damage associated molecular patterns (DAMPS) as well as in in vivo studies involving orthotopic heart transplantation and kidney transplantation. Cytokine adsorption has been used successfully in clinical applications to both heart and kidney transplantation.

The present study is a randomized controlled study which aims to collect preliminary data on the efficacy of a medical device through the comparison of patients undergoing LTx with and without cytokine adsorption.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Eligibility to undergo double lung transplantation at either trial site

Exclusion criteria

  • Age <18 years
  • Previous organ transplantation
  • Presence of any conditions at the time of surgery that require immunosuppressive therapy. Immunosuppressive therapy is defined as:
  • Cyclosporine, Tacrolimus, Everolimus, or Sirolimus, minimum 1 month of treatment prior to transplantation and active treatment at the time of transplantation.
  • Any form of antibody-based treatment that is known for having an immunomodulatory effect taken up to 1 week before transplantation.
  • Non-consent

Treatment and study plan

Device: CytoSorb

Device

Medical device used hemoperfusion and cytokine adsorption in conjunction with lung transplantation.

Primary outcomes

  1. To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation.

    Time frame: First 72 hours after lung transplantation

    Higest value of oxygenation expressed as the PaO2/FiO2 ratio.

  2. To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 24 hours

    Time frame: 24 hours after lung transplantation

    Oxygenation expressed as the PaO2/FiO2 ratio at 24 hours

  3. To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 48 hours

    Time frame: 48 hours after lung transplantation

    Oxygenation expressed as the PaO2/FiO2 ratio at 48 hours

  4. To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 72 hours

    Time frame: 72 hours after lung transplantation

    Oxygenation expressed as the PaO2/FiO2 ratio at 72 hours

Secondary outcomes

  1. To determine whether cytokine reduction by cytokine filtration improves levels of plasma inflammatory markers (including cytokines) in patients undergoing lung transplantation.

    Time frame: 0-72 hours (0-3 days) after lung transplantation

    Plasma levels of inflammatory markers: interleukin (IL)-10, IL-1β, soluble IL-2 receptor, IL-6, IL-8, and tumour necrosis factor (TNF)α before and immediately after transplantation and at 6, 12, 24, 48, and 72 hours after transplantation, and C-reactive protein (CRP) and white blood cells before and immediately after transplantation and at day 1, 2, and 3 after transplantation

  2. To determine whether cytokine reduction by cytokine filtration decreases lung infiltrates and oedema in patients undergoing lung transplantation

    Time frame: 0-72 hours (0-3 days) after lung transplantation

    Infiltrates and oedema measured by chest x-ray and/or CT scan of the thorax at day 1, 2, and 3 after transplantation

  3. To determine whether cytokine reduction by cytokine filtration improves arterial blood gas measures in patients undergoing lung transplantation

    Time frame: 0-72 hours (0-3 days) after lung transplantation

    Highest daily arterial blood gas measurements recorded on day 1, 2, and 3 after transplantation, as a measure of lung function

  4. To determine whether cytokine reduction by cytokine filtration decreases severity of primary graft dysfunction (PGD) in patients undergoing lung transplantation

    Time frame: 0-72 hours (0-3 days) after lung transplantation

    PGD severity as evaluated per standard clinical procedures using a rating scale from 0-3 on day 1, 2, and 3 after transplantation, as a measure of lung function

  5. To determine whether cytokine reduction by cytokine filtration decreases incidence of primary graft dysfunction (PGD) in patients undergoing lung transplantation

    Time frame: 0-72 hours (0-3 days) after lung transplantation

    Presence of any grade of PGD on day 1, 2, and 3 after transplantation, as a measure of lung function

  6. To determine whether cytokine reduction by cytokine filtration decreases need for norepinephrine in patients undergoing lung transplantation

    Time frame: 0-72 hours (0-3 days) after lung transplantation

    Total dose of norepinephrine administered in the first 72 h

  7. To determine whether cytokine reduction by cytokine filtration decreases mortality in patients undergoing lung transplantation

    Time frame: First 4 years

    Mortality up to 48 months after transplantation

  8. To determine whether cytokine reduction by cytokine filtration improves diffusion capacity of the lungs (DLCO) in patients undergoing lung transplantation

    Time frame: First 4 years

    Lung diffusion capacity, measured by carbon monoxide (CO) diffusion, at 6, 12, 24, and 48 months after transplantation, as a measure of lung function

  9. To determine whether cytokine reduction by cytokine filtration improves forced expiratory volume (FEV1), forced vital capacity (FVC), and total lung capacity in patients undergoing lung transplantation

    Time frame: First 4 years

    Forced expiratory volume (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) measured by spirometry at 1, 3, 6, 12, 24 and 48 months after transplantation, as a measure of lung function

  10. To determine whether cytokine reduction by cytokine filtration improves occurrence of any acute rejection episodes in patients undergoing lung transplantation

    Time frame: First 4 years

    Occurrence of any acute rejection episodes (clinically treated and/or biopsy verified) up to 48 months after transplantation, as a measure of lung function

  11. To determine whether cytokine reduction by cytokine filtration improves Chest CT in patients undergoing lung transplantation

    Time frame: First 4 years

    Chest CT findings at 1, 3, 6, 12, 24, 36 and 48 months after transplantation

  12. To determine whether cytokine reduction by cytokine filtration improves presence of any CLAD in patients undergoing lung transplantation

    Time frame: First 4 years

    Presence of any CLAD and CLAD subtypes up to 48 months after transplantation, as a measure of lung function

  13. To determine whether cytokine reduction by cytokine filtration improves kidney function in patients undergoing lung transplantation

    Time frame: First 4 years

    Kidney function evaluated by measurement of serum creatinine levels; calculated glomerular filtration rate (GFR); and need for renal replacement therapy on day 1, 2, and 3 and at 1, 3, 6, 9, 12, 24, and 48 months after transplantation; urea levels on day 1, 2, and 3 after transplantation; and iohexol clearance at 3, 6, 9, 12, 24, 36, and 48 months after transplantation

  14. To determine whether cytokine reduction by cytokine filtration improves quality of life (QOL) in patients undergoing lung transplantation

    Time frame: First 4 years

    QOL evaluated by the 36-Item Short Form Health Survey (SF-36) at 24 and 48 months after transplantation

Other outcomes

  1. Safety endpoints

    Time frame: First 72 hours after transplantation

    Adverse events in the first 72 hours after transplantation. Thus, the aim of this clinical trial is to determine the efficacy of cytokine filtration in improving successful LTx rates, based on its effects on oxygenation ratio, pulmonary function, PGD, kidney function, CLAD, and survival. These outcomes will also be analysed on the molecular, and tissue levels to identify the mechanisms by which cytokine filtration promotes the acceptance of lung transplants. The primary outcome will be oxygenation ratio, defined as the highest PaO2/FiO2 (P/F) within 72 h after LTx.

  2. Exploratory endpoints

    Time frame: First 4 years

    Collection of a portion of routinely collected transplanted lung tissue by transbronchial biopsy and bronchoalveolar lavage fluid (at least at 1, 3 and 12 months, with additional timepoints if clinically indicated), collection of explanted recipient lung tissue, and collection of blood samples (at least before transplantation; immediately after transplantation; 6, 12, 24, 48, and 72 hours; 1 and 2 weeks; and 1, 3, 6, 9, 12, 24, 36, and 48 months after transplantation, with additional timepoints if clinically indicated) in a biobank for future exploratory analyses.

Study contacts

Contact information is provided by the study sponsor or research team.

Jesper Magnusson, MD, PhD

CONTACT

[email protected]

Sandra Lindstedt, MD,PhD

CONTACT

[email protected]

+46737220580

Sponsors and collaborators

Lead sponsor

Lund University Hospital

Other

Registry information

Official study title

Cytokine Filtration in Lung Transplantation - a Randomised, Controlled, Multicentre Clinical Trial (GLUSorb)

Important dates

Study start
2023
Primary completion
2027
Study completion
2029
First posted
Sep 2, 2022
Registry last updated
Sep 18, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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